基质金属蛋白酶抑制剂的电离状态对基于对接的抑制剂设计的影响。
The impact of ionization States of matrix metalloproteinase inhibitors on docking-based inhibitor design.
作者信息
Zhong Haizhen, Wees Melissa A, Faure Theresa D, Carrillo Carol, Arbiser Jack, Bowen J Phillip
机构信息
Department of Chemistry, University of Nebraska at Omaha , DSC362, 6001 Dodge Street, Omaha, Nebraska 68182, United States.
Department of Dermatology, School of Medicine, Emory University , Atlanta, Georgia 30322, United States.
出版信息
ACS Med Chem Lett. 2011 Mar 29;2(6):455-60. doi: 10.1021/ml200031m. eCollection 2011 Jun 9.
Abstract
The influence of ionization states of hydroxamates and retrohydroxamates and the presence of zinc ions in the active site were investigated using the wild-type and E402Q mutant of MMP-9. The deprotonated hydroxamates showed a significantly enhanced enrichment factor in the presence of zinc ions. A pharmacophore model was developed based on the deprotonated compounds and was used to identify four structurally diverse compounds with antiproliferative activities.
摘要
使用基质金属蛋白酶-9（MMP-9）的野生型和E402Q突变体，研究了异羟肟酸和逆异羟肟酸的电离状态以及活性位点中锌离子的存在所产生的影响。在锌离子存在的情况下，去质子化的异羟肟酸显示出显著增强的富集因子。基于去质子化的化合物构建了一个药效团模型，并用于鉴定四种具有抗增殖活性的结构多样的化合物。
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